Objective:: This study was designed to demonstrate that four weeks of fluticasone propionate (FP) 100 micrograms (mcg) combined with salmeterol 50 mcg twice daily (BID) via DISKUS® resulted in protection against bronchospasm induced by activity, as measured by standardized exercise challenge testing in pediatric and adolescent subjects who required regular use of inhaled corticosteroids for the treatment of persistent asthma. Methods:: Prior to study entry, all patients reported regular use of inhaled corticosteroids (ICS). During screening all patients demonstrated ≥20% fall in FEV1 following exercise. Results:: A total of 231 subjects aged 4 to 17 were randomized to the two study treatments: 113 to the FP/salmeterol combination group (FSC) and 118 to receive FP 100 mcg BID. Of the subjects randomized, 106 (94%) subjects in the FSC 100/50 group and 108 (92%) subjects in the FP 100 group completed the study. At the end of treatment (Week 4), both FSC and FP protected against a fall in FEV1 following exercise in patients who at baseline experienced ≥20% fall in FEV1 following exercise. A mean decrease in FEV1 of 9.9% was observed in the FSC 100/50 group as compared with a mean decrease of 11.1% in the FP 100 group; there was no statistical difference between treatments. Conclusion:: Both FSC 100/50 and FP 100 provided protection against an exercised-induced fall in FEV1; but statistically significant differences we not noted. Both treatments were well-tolerated over four weeks and FSC 100/50 had an adverse event profile comparable to that observed with FP 100.